Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/ijms18102048
Keywords
multiple sclerosis; B cells; antibodies; antigen presenting cells; anti-CD20; plasma cells; B cell therapies; experimental autoimmune encephalomyelitis; regulatory B cells
Funding
- Deutsche Forschungsgemeinschaft (German Research Foundation) [EXC 1010 SyNergy, SFB/Transregio 128/2-A4]
- National Multiple Sclerosis Scociety [FG 2067-A-1]
- Oppenheim Award for Multiple Sclerosis
- National Multiple Sclerosis Society (NMSS) [PP 1660]
- Deutsche Forschungsgemeinschaft (DFG) [WE 3547/5-1]
- Novartis
- TEVA
- Biogen-Idec
- Roche
- Merck
- ProFutura Programm of the Universitatsmedizin Gottingen
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B cells, plasma cells and antibodies may play a key role in the pathogenesis of multiple sclerosis (MS). This notion is supported by various immunological changes observed in MS patients, such as activation and pro-inflammatory differentiation of peripheral blood B cells, the persistence of clonally expanded plasma cells producing immunoglobulins in the cerebrospinal fluid, as well as the composition of inflammatory central nervous system lesions frequently containing co-localizing antibody depositions and activated complement. In recent years, the perception of a respective pathophysiological B cell involvement was vividly promoted by the empirical success of anti-CD20-mediated B cell depletion in clinical trials; based on these findings, the first monoclonal anti-CD20 antibodyocrelizumabis currently in the process of being approved for treatment of MS. In this review, we summarize the current knowledge on the role of B cells, plasma cells and antibodies in MS and elucidate how approved and future treatments, first and foremost anti-CD20 antibodies, therapeutically modify these B cell components. We will furthermore describe regulatory functions of B cells in MS and discuss how the evolving knowledge of these therapeutically desirable B cell properties can be harnessed to improve future safety and efficacy of B cell-directed therapy in MS.
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